Pulmonary Aspergillosis

Transcription

1 May 2005 Pulmonary Aspergillosis Nancy Wei, Harvard Medical School, Year III

2 Overview Pulmonary aspergillosis background information Patient presentations Common radiographic findings for each type of pulmonary aspergillosis Summary 1

3 Aspergillus: the Facts Aspergillus - a fungus that is ubiquitous in the soil. It has low pathogenicity, therefore affected patients have either underlying chronic lung disease and/or impaired immunity. Manifestations of pulmonary aspergillosis depend on the virulence and number of spores inhaled, on the patient s immune status, and on the presence of any underlying chronic lung disease. Franquet et al. Radiographics

4 The 4 Types of Pulmonary Aspergillosis 1. Saprophytic aspergillosis (aspergilloma/mycetoma) 2. Hypersensitivity reaction (allergic bronchopulmonary aspergillosis) 3. Semi-invasive (chronic necrotizing) aspergillosis 4. Angioinvasive aspergillosis 3

5 Patient 1 Mr. H. History: Mr. H. is a 46 y.o. man with h/o end-stage renal disease secondary to amyloidosis s/p living donor related renal transplant, sarcoidosis, and hepatitis B, C, and D who p/w non-productive cough and dyspnea x 2 weeks. He denies fevers, chills, sick contacts, or recent travel. He has been taking all of his immunosuppressive medications (CellCept, Prednisone, Prograf, Valcyte) regularly. He smokes 0.5 packs/day. Past IVDU. Denies EtOH use. Physical Exam: Afebrile, RR 32, O2sat 95% on RA, sharp barking cough, bilateral posterior inspiratory crackles. Labs: WBC 1.8, ANC

6 Mr. H. s Radiograph Scarring and pleural thickening of the lung apices Superior retraction and fullness of the hila bilaterally Blunting of the left costophrenic angle Patchy opacities scattered throughout both lungs. PACS, BIDMC All findings secondary to sarcoidosis and stable from CXR taken within the last 2 years. 5

7 A Closer Look at the Apices Nodular opacification surrounded by air PACS, BIDMC 6

8 Mr. H. s Chest CT Cyst in the left apex with rounded soft tissue opacity surrounded by a crescent of air. Enlarged paratracheal/bronchial lymph nodes L>R ground glass opacification at the apices with pleural thickening. PACS, BIDMC All findings are stable from previous chest CT except for the soft tissue opacity with air crescent sign in the L apex. 7

9 Differential Diagnosis Air-crescent sign Aspergilloma/mycetoma Angioinvasive aspergillosis (during recovery) Tuberculosis Tuberculous cavity with a Rasmussen aneurysm Lung abscess Pneumocystis carinii pneumonia Cavitating bronchogenic carcinoma Hematoma (A. Khan et al. Curr Probl Diagn Radiol, July/August 2003) 8

10 Narrowing the Ddx: Sputum culture was positive for Aspergillus species, all other cultures/stains (TB, PCP, RSV Ag) were negative. Diagnosis: Aspergilloma (a.k.a.mycetoma, fungus ball) or angioinvasive aspergillosis during the recovery phase. Given the patient s history of sarcoidosis and ANC of >1000, it was felt that the radiographic finding is more likely aspergilloma. 9

11 Aspergilloma Aspergillus colonization of preexisting cavities to form a mycetoma (a fungal mass). The most common underlying causes are tuberculosis, sarcoidosis and bronchiectasis. The host is typically immunocompetent. Sometimes associated with bronchogenic cyst, pulmonary sequestration, pneumatoceles secondary to PCP in AIDS patients. Clinical manifestation chronic cough, hemoptysis Treatment: 10% resolve spontaneously, anti-fungal medication (fluconazole, itraconazole, or IV amphotericin B) Surgical resection for patients with severe life-threatening hemoptysis or selective bronchial artery embolization 10

12 Patient 2 Mr. R. History: Mr. R. is a 73 y.o. man with history of transfusion dependent AML with chronic neutropenia x 2yrs, who presents with non-productive cough x 6 months, worse in the evenings. No improvement with short courses of Azithromycin or Levaquin. Denies fevers, chills, night sweats. Non-smoker, no EtOH use Physical Exam: VS: T 98.8 F, BP 139/71, P 120, RR 20, O2 sat 96% RA Chest: clear to auscultation Labs: WBC 2.3, 8% Neutrophils, ANC

13 Relation of Absolute Neutrophil Count to Risk of infection UpToDate v

14 Mr. R. s Chest CT Enlarged subcarinal lymph nodes Bilateral Pleural Effusion PACS, BIDMC 13

15 Mr. R. s Chest CT Left lung major fissure with pleural thickening/fluid Multifocal rounded consolidations with irregular margins and surrounded by a halo of groundglass opacification Wedge shaped consolidation along the R major fissure surrounded by groundglass opacification. PACS, BIDMC 14

16 Differential Diagnosis The differential for multiple nodules with ground-glass halo on CT should include any process that could cause hemorrhage around multiple nodules or infarcts. Angioinvasive aspergillosis Infection by TB, Mucorales, Candida, herpes simplex, and Cytomegalovirus Wegener s granulomatosis Kaposi sarcoma Hemorrhagic metastases Bronchoalveolar carcinoma (A. Khan et al. Curr Probl Diagn Radiol, July/August 2003) 15

17 Narrowing the DDx Pt was taken to bronchoscopy and for VATS. Pathology of a wedge resection of the right lower lobe showed necrotizing and organizing fungal pneumonitis, with fungal morphology consistent with Aspergillus species. Diagnosis: invasive pulmonary aspergillosis 16

18 Angioinvasive aspergillosis Occurs almost exclusively in immunocompromised patients with severe neutropenia. Pathology: invasion and occlusion of small to mediumsized pulmonary arteries by fungal hyphae leading to formation of necrotic hemorrhagic nodules or pleurabased, wedge-shaped hemorrhagic infarcts. Clinical manifestations: cough, pleuritic chest pain, hemoptysis Treatment: long-term antifungal medications, surgical resection 17

19 Angioinvasive Aspergillosis on HRCT Findings Ill-defined nodules or focal consolidation with a halo sign (early) Cavitary nodules with air-crescent sign (late) HRCT is more sensitive in detecting nodules suggestive of fungal infection earlier in immunocompromised patients than radiograph and BAL culture. Bronchoscopy and VATS are often not an option in severely immunocompromised patients. Early detection and treatment with antifungal or surgical resection dramatically improve the prognosis of patients with angioinvasive aspergillosis. 18

20 Chronic Necrotizing Aspergillosis Tissue necrosis and granulomatous inflammation (similar to that seen in reactivation TB), due to growth in the alveolar spaces with hemorrhage and bronchial wall invasion. No angioinvasion. Most commonly seen in patients with chronic debilitating illness (i.e. advanced age, diabetes, poor nutrition, alcoholism, steroid treatment). Clinical manifestations: insidious in nature. Chronic cough, sputum production, fever, weight loss, anorexia, hemoptysis. Diagnosis: abnormal findings on radiography and bronchoscopic biopsy consistent with tissue invasion Treatment: long-term antifungal medication 19

21 Radiographic findings of chronic necrotizing aspergillosis CXR: Slowly progressive upper lobe consolidation predominantly with cavitation or pleural thickening, and multiple nodular areas of increased opacity. Khan, A. Curr Probl Diagn Radiol,

22 Radiographic findings of chronic necrotizing aspergillosis CT: cavitation with bronchial wall thickening and bronchial obstruction with obstructive pneumonitis or collapse. DDx of thickening and narrowing of a central bronchus: mucormycosis, tuberculosis, amyloidosis, and sarcoidosis. Franquet, T. Radiographics

23 Allergic Bronchopulmonary Aspergillosis Most commonly seen in patient with long-standing asthma or cystic fibrosis. Complex hypersensitivity reaction to Aspergillus with immune complex deposition in the bronchial mucosa leading to necrosis and eosinophilic infiltrates with damage, resulting in bronchial dilation of the segmental and subsegmental bronchi Clinical manifestations: recurrent wheezing, low-grade fever, cough, sputum production. H/o recurrent pneumonia. Diagnosis: asthma, eosinophilia, elevated IgE, + skin test, pulmonary infiltrates and central bronchiectasis on CXR/CT. Treatment: corticosteroids 22

24 Radiographic findings in allergic bronchopulmonary aspergillosis CXR - homogeneous, tubular, finger-in-glove areas of increased opacity in a bronchial distribution Khan, A. Curr Probl Diagn Radiol,

25 Radiographic findings in allergic bronchopulmonary aspergillosis On CT mucoid impaction and bronchiectasis involving the segmental and subsegmental bronchi of the upper lobes. 30% have high attenuation or calcification of the mucus plugs. Franquet, T. Radiographics 2001 Ddx: other causes of mucoid impaction (i.e. endobronchial lesions, bronchial atresia, bronchiectasis). 24

26 Summary There are 4 pulmonary manifestations of aspergillosis: saprophytic, allergic bronchopulmonary, chronic necrotizing, and angioinvasive. Aspergillosis typically affects patients with chronic lung disease and immunocompromised individuals. The different manifestations are dependent on the immune status of the patient. Soubani, A. O. et al. Chest 2002;121:

27 Summary Air-crescent sign on CT or CXR is associated with aspergilloma in immunocompetent patients and with recovery from angioinvasive aspergillosis in immunosuppressed patients. CT halo sign indicates a rim of hemorrhage around a nodule/infarct and is highly associated with angioinvasive aspergillosis in immunosuppressed patients. Allergic bronchopulmonary aspergillosis is the result of a hypersensitivity reaction to Aspergillus in an immunocompetent patient, not an infection. 26

28 References Baehner, R. Neutropenia associated with Infections. UpToDate 2005, v Collins, J. CT Signs and Patterns of Lung Disease. Radiology Clinics of North America 2001; 39: Franquet, T. et al. Spectrum of Pulmonary Aspergillosis: Histologic, Clinical, and Radiologic Findings. Radiographics 2001; 21: Kenney, H., G. Agrons, J. Shin. Best Cases from the AFIP. Invasive Pulmonary Aspergillosis: Radiologic and Pathologic Findings. Radiographics 2002; 22: Khan, A., C. Jones, and S. Macdonald. Bronchopulmonary Aspergillosis: A Review. Current Problems in Diagnostic Radiology 2003; 32: Soubani, A. and P. Chandrasekar. The Clinical Spectrum of Pulmonary Aspergillosis. Chest 2002; 121: Webb, W.R., N. Muller, and D. Naidich. High-Resolution CT of the Lung 3 rd ed. Lippincott Williams and Wilkins,

29 Acknowledgements Jesse Wei, MD Pamela Lepkowski Larry Barbaras 28